Ltured human breast cells. Retrovirology 2007, 4:73. 51. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 Kent WJ: BLAT he BLAST-like alignment tool. Genome Res 2002, 12:656?64. 52. Chan HH, Tsai SJ, Sun HS: http://www.binfo.ncku.edu.tw/TAG/GeneDoc.php. 53. Giardine B, Riemer C, Hardison RC, Burhans R, Elnitski L, Shah P, Zhang Y, Blankenberg D, Albert I, Taylor J, Miller W, Kent WJ, Nekrutenko A: Galaxy: a platform for interactive large-scale genome analysis. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27872238 Genome Res 2005, 15:1451?455.doi:10.1186/1742-4690-11-34 Cite this article as: Konstantoulas and Indik: Mouse mammary tumor virus-based vector transduces non-dividing cells, enters the nucleus via a TNPO3-independent pathway and integrates in a less biased fashion than other retroviruses. Retrovirology 2014 11:34.
Sokol et al. Retrovirology 2014, 11:36 http://www.retrovirology.com/content/11/1/RESEARCHOpen AccessNovel principles of gamma-retroviral insertional transcription activation in murine leukemia virus-induced end-stage tumorsMartin Sokol1, Matthias Wabl2, Irene Rius Ruiz1 and Finn Skou Pedersen1*AbstractBackground: Insertional mutagenesis screens of retrovirus-induced mouse tumors have proven valuable in human cancer research and for understanding adverse effects of retroviral-based gene therapies. In previous studies, the assignment of mouse genes to individual retroviral integration sites has been based on close proximity and expression patterns of annotated genes at target positions in the genome. We here employed next-generation RNA sequencing to map retroviral-mouse chimeric junctions genome-wide, and to identify local patterns of transcription activation in T-lymphomas induced by the murine leukemia gamma-retrovirus SL3-3. Moreover, to determine epigenetic integration preferences underlying long-range gene activation by retroviruses, the colocalization propensity with common epigenetic enhancer markers (H3K4Me1 and H3K27Ac) of 6,117 integrations derived from end-stage tumors of more than 2,000 mice was examined. Results: We detected several novel mechanisms of retroviral insertional mutagenesis: bidirectional activation of mouse transcripts on opposite sides of a provirus including transcription of unannotated mouse sequence; sense/antisense-type activation of genes located on opposite DNA strands; BMS-214662MedChemExpress BMS-214662 tandem-type activation of distal genes that are positioned adjacently on the same DNA strand; activation of genes that are not the direct integration targets; combination-type insertional mutagenesis, in which enhancer activation, alternative chimeric splicing and retroviral promoter insertion are induced by a single retrovirus. We also show that irrespective of the distance to transcription start sites, the far majority of retroviruses in end-stage tumors colocalize with H3K4Me1 and H3K27Ac-enriched regions in murine lymphoid tissues. Conclusions: We expose novel retrovirus-induced host transcription activation patterns that reach beyond a single and nearest annotated gene target. Awareness of this previously undescribed layer of complexity may prove important for elucidation of adverse effects in retroviral-based gene therapies. We also show that wild-type gamma-retroviruses are frequently positioned at enhancers, suggesting that integration into regulatory regions is specific and also subject to positive selection for sustaining long-range gene activation in end-stage tumors. Altogether, this study should prove useful for extrapolating adverse outcomes of retroviral vector therapies, and for understanding fundamental c.